Acetaminophen is a widely used over-the-counter analgesic (pain reliever) and antipyretic (fever reducer). It is commonly used for the relief of fever, headaches, and other minor aches and pains, and is a major ingredient in numerous cold and flu remedies. In combination with non-steroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics, acetaminophen is used also in the management of more severe pain (such as postoperative pain).
One of the problems in the development of an injectable acetaminophen is its poor solubility in water. One approach to improve solubility is to glycosylate acetaminophen. For example, glycosylated acetaminophen pro-drug analogs that with an olefin at the 2,3 position of the carbohydrate are described in U.S. Pat. No. 5,693,767 [1] shown in FIG. 1.
Acetaminophen is most stable at pH 6, and the analogs with the olefin at the 2,3 position, will hydrolyze easily at this and lower pH's. Thus, new acetaminophen analogs that are more stable to pH's lower than 7 are needed.